Acute lung injury is a feature of sepsis, systemic inflammatory response, and adult respiratory distress syndrome. Non-cardiogenic pulmonary edema and impaired gas exchange are consequences of acute lung injury, irrespective of etiology. The mechanisms causing pulmonary edema due to acute lung injury are not well understood. Ischemia-reperfusion injury (IRI), a form of acute lung injury occurring immediately following lung transplantation, is a frequent complication causing morbidity and mortality. See King et al., Ann. Thorac. Surg., 69, 1681-1685 (2000).
Reperfusion following an interval of ischemia results in an inflammatory response involving components of the innate immune system, including the complement and coagulation cascades. Both parenchymal and myeloid cells elaborate free radicals, nitric oxide, and pro- and anti-inflammatory cytokines. See de Perrot et al., Am. J. Respir. Crit. Care Med., 167(4), 490-511 (2003); de Groot and Rauen, Transplant Proc., 39(2), 481-484 (2007); and Mollen et al., Shock, 26(5), 430-437 (2006).
A greater understanding of lung IRI is likely relevant to many types of acute lung injury, and can be of benefit to substantial numbers of patients, in addition to lung transplant recipients. Such knowledge can also potentially be used to facilitate the retrieval of lungs from non-heart-beating cadaver donors for transplant, and/or assist in the salvage of sub-transplant quality lungs, See Steen et al. Ann Thorac Surg., 83, 2191-2195 (2007) thereby addressing the critical shortage of transplantable lungs. See Egan et al., Ann. Thorac. Surg., 52, 1113-1121 (1991) and Egan, J. Heart Lung Transplant., 23(1), 3-10 (2004).